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CRISPR-Cas9: Not Just Another Scientific Revolution

Poised to transform the world as we know it, a new gene-editing system has bioethicists wringing their hands, physicians champing at the bit, and researchers dueling with demons.

Is it possible to overstate the potential of a new technology that efficiently and cheaply permits deliberate, specific, and multiple genomic modifications to almost anything biological? What if that technology was also capable of altering untold future generations of nearly any given species—including the one responsible for creating it? And what if it could be used, for better or worse, to rapidly exterminate an entire species?

Certain experts have no intention of veiling their enthusiasm—or their unease. Consider, for example, biologist David Baltimore, who recently chaired an international summit dedicated primarily to the technology’s much-disputed ethical implications. “The unthinkable has become conceivable,” he warned his audience in early December. Powerful new gene-editing techniques, he added, have placed us “on the cusp of a new era in human history.”

If so, it might seem somewhat anticlimactic to note that Science magazine dubbed this technology its “Breakthrough of the Year” for 2015, or that its primary developers are widely considered shoo-ins for a Nobel Prize— in addition, that is, to the $3 million Breakthrough Prize in Life Sciences already earned by two such researchers. All of which might sound trifling compared to the billions up for grabs following imminent resolution of a now-vicious patent dispute.

Although no geneediting tool has ever inspired so much drama, the new technology’s promise as a practical remedy for a host of dreadful diseases, including cancer, remains foremost in researchers’ minds. Eager to move beyond in vitro and animal model applica tions to the clinical setting, geneticists across the globe are quickly developing improved molecular components and methods to increase the technology’s accuracy. In case you haven’t heard, a truly profound scientific insurrection is well underway.

Adapting CRISPR-Cas9

“Think about a film strip. You see a particular segment of the film that you want to replace. And if you had a film splicer, you would go in and literally cut it out and piece it back together—maybe with a new clip. Imagine being able to do that in the genetic code, the code of life.”—Biochemist Jennifer Doudna (CBS News 2015)

Genetic manipulation is nothing new, of course. Classic gene therapy, for example, typically employs a vector, often a virus, to somewhat haphazardly deliver a healthy allele somewhere in the patient’s genome, hopefully to perform its desired function wherever it settles. Alternatively, RNA interference selects specific messenger RNA molecules for destruction, thus changing the way one’s DNA is transcribed. Interference occurs, however, only so long as the damaging agent remains within the cell.

Contemporary editing techniques, on the other hand, allow biologists to actually alter DNA—the “code of life,” as Doudna suggests—and to do so with specific target sequences in mind. The three major techniques have much in common. Each involves an enzyme called a “programmable nuclease,” for example, which is guided to a particular nucleotide sequence to cleave it.

Then, in each case, the cell’s machinery quickly repairs the double-stranded break in one of two ways. Non-homologous end joining for gene “knock out” results when reconstruction—usually involving small, random nucleotide deletions or insertions—is performed only by the cell. Here, the gene’s function is typically undermined. By contrast, homology-directed repair for gene “knock in” occurs when the cell copies a researcher’s DNA repair template delivered along with the nuclease. In this case, the cleaved gene can be corrected, or a new gene or genes can be inserted (Corbyn 2015).

But in other ways, the three editing techniques are very distinct. Developed in the late 1990s and first used in human cells in 2005, zinc-finger nucleases (ZFN) attach cutting domains derived from the prokaryote Flavobacterium okeanokoites to proteins called “zinc fingers” that can be customized to recognize certain three-base-pair DNA codes. Devised in 2010, transcription activator-like effector nucleases (TALENs) fuse the same cutting domains to different proteins called TAL effectors. For both ZFN and TALENs, two cutting domains are necessary to cleave double-stranded DNA (Maxmen 2015).

About Skeptical Inquirer

Creators of the Paranormal:
A handful of twentieth-century figures “created”
the modern concept of the paranormal and its
leading topics, transporting fantasy, myth, or
speculation into a kind of believable “reality.”
Most proved to be a chimera.
CRISPR-Cas9:
Not Just Another
Scientific Revolution
Dissociation
and Paranormal Beliefs
Scientific Reasoning at
the USAF Academy:
An Examination into
Titanium-Treated Necklaces
Stick It In Your Ear!
How Not To Do Science
A Testament of Belief
Masquerading as Science
and much more...